Brain perfusion imaging with single-photon emission computerized tomography is a method of assessing regional perfusion, i.e., the quantities of blood distributed to various parts of the brain. The data generated provides information which is useful for determining metabolic activity in various parts of the brain, for example in assessing the effects of stroke. Its successful application requires imaging agents which can be administered intravenously, and which pass the blood-brain barrier to enter brain tissue.
Useful brain imaging agents require a radioactive element and structure which causes the agent to be transported in the blood, to pass from the blood across the blood-brain barrier and to be retained in brain tissue sufficiently long to measure its concentrations in various parts of the brain. Desirably, 100% of the imaging agent which flows to a particular part of the brain is absorbed into brain tissue, and that agent remains in the brain tissue for about four to six hours so that its concentration (and therefore the amount of blood which flowed to that part of the brain) can be determined. Initial consideration was given to compounds containing radioactive isotopes of iodine and selenium, i.e., I-123, I-125, I-131 and Se-75. Selenium-75 gives poor imaging characteristics; its radiation levels are too high and its half-life is too long. Therefore it can expose patients to the risk of excessive doses of radiation. Iodine-131 suffers from the same difficulties. Iodine-125 has too long a half-life and too low gamma intensity. Iodine-123 is useful, and has been the subject of preliminary clinical studies in the form of N-isopropyl-p-[I-123]iodoamphetamine which provided remarkable results. However I-123 is very expensive and not readily available. Therefore, attention has turned to compounds based on technetium-99m which has the same advantages as Iodine-123, and which is relatively inexpensive and readily available; it is currently the radionuclide which is most widely used for a variety of diagnostic nuclear imaging procedures.
Investigations have been conducted using technetium-99m-labeled 1,2-dithia-5,8-diazacyclodecane, and the results were reported by Kung et al in The Journal of Nuclear Medicine, Vol. 25 pages 326-332. These compounds were found to effectively cross the blood-brain barrier. However, they are retained in brain tissue for only relatively short times.